Internalization of the insulin receptor has been examined in isolated rat adipose cells at 37 C. The results suggest that 1) insulin induces a rapid translocation of both major subunits of its own receptor from the plasma membrane into at least two different intracellular membrane compartments, 2) this translocation occurs without receptor loss or alterations in receptor subunit structure, 3) the 135K receptor subunit is primarily, if not exclusively, exposed on the extracellular surface of the plasma membrane, and this vectorial disposition is inverted during translocation, and 4) this translocation represents internalization of the insulin receptor through an endocytic-like process. A specific D-glucose-inhibitable cytochalasin B binding assay for glucose transporters has been used to provide preliminary evidence that 1) insulin's stimulatory action on glucose transport in isolated rat adipose cells occurs through a subcellular redistribution of glucose transporters rapidly cycling in an exocytic/endocytic-like fashion, 2) insulin acts at a step whereby glucose transporters associated with the plasma membrane become functional, and 3) cAMP-mediated counterregulation of insulin-stimulated glucose transport by catecholamines comprises both the regulation of the subcellular distribution of glucose transporters and the modulation of the activity of those glucose transporters present in the plasma membrane. Insulin also appears to stimulate glucose transport in isolated guinea pig and human adipose cells, and rat diaphragm through this same translocation mechanism. The effects of chronic insulin administration have been studied. The results suggest that chronic hyperinsulinemia increases insulin binding and the capacity or rat adipose cells, but not muscle, to metabolize glucose without changing the cells' sensitivity to insulin. Increased glucose utilization results from both increased transport and increased intracellular glucose metabolism. The mechanism of insulin-stimulated IGF-II binding has been examined in the isolated rat adipose cell. The results suggest that 1) IGF-II receptors rapidly cycle between the plasma membrane and a low-density microsomal pool, and 2) insulin stimulates IGF-II binding through a redistribution of receptors of constant Ka from this pool to the plasma membrane.